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Publication : Tackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis.

First Author  Boura-Halfon S Year  2024
Journal  Methods Mol Biol Volume  2713
Pages  481-503 PubMed ID  37639143
Mgi Jnum  J:361140 Mgi Id  MGI:7856479
Doi  10.1007/978-1-0716-3437-0_32 Citation  Boura-Halfon S, et al. (2024) Tackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis. Methods Mol Biol 2713:481-503
abstractText  Macrophages represent a broad spectrum of distinct, but closely related tissue-resident immune cells. This presents a major challenge for the study of functional aspects of these cells using classical Cre recombinase-mediated conditional mutagenesis in mice, since single promoter-driven Cre transgenic models often display limited specificity toward their intended target. The advent of CRISPR/Cas9 technology has now provided a time- and cost-effective method to explore the full potential of binary transgenic, intersectional genetics. Specifically, the use of two promoters driving inactive Cre fragments that, when co-expressed, dimerize and only then gain recombinase activity allows the characterization and manipulation of genetically defined tissue macrophage subpopulations. Here, we will elaborate on the use of this protocol to capitalize on these recent technological advances in mouse genetics and discuss their strengths and pitfalls to improve the study of tissue macrophage subpopulations in physiology and pathophysiology.
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